No description available.

Repeated administration of ochratoxin A (OTA) caused renal morphological dose-related changes, that were associated with proximal tubular and glomerular damage the latter showing oedema and prominent PAS staining suggestive of glomerular basement membrane thickening. On the other hand, the combined administration of repeated doses of OTA and aflatoxin B[1] (2. 5 mg and 100 ug per kg, respectively), appeared to have a synergistic effect, characterized by severe disruption of proximal tubules and general morphological derrangement of the glomerulus, involving intense and faint staining nuclei (suggestive of cell necrosis) and cytoplasmic vacuolation, which was not seen with either toxin alone. When clinical biochemical parameters were measured after repeated administration of a low dose of OTA, enzymuria, glucosuria, polyuria and proteinuria were observed, with glucose and alkaline phosphatase as the most sensitive parameters. Metabolic studies performed in vitro showed that isolated pig and rat glomeruli incorporate different amino acids linearly for several hours at different rates and perform oxidative metabolism of glucose and fatty acids to CO[2] also linearly. For pig glomeruli the order of amino acid incorporation was LEU >> PRO = HIS > LYS > GLY and for rat glomeruli it was TRP >> PHE > TYR = LEU > PRO > HIS. The same amino acids were incorporated in a similar way in rat tubules, but the incorporation rate is 10-fold lower. When de novo synthesis of protein by pig glomeruli exposed to different chemicals was assessed, using proline (PRO) as the precursor, adriamycin (ADR) and ethacrynic acid (ETA) inhibited protein synthesis more than 2-bromoethanamine (BEA) and streptomycin (STR), and much more than puromycin aminonucleoside (PAN). When isolated rat glomeruli were exposed to low concentrations of OTA, there was a generalized inhibition on de novo synthesis of protein from the six amino acids tested and the aromatic amino acids (TRP, TYR and PHE) were more sensitive to OTA effect than PRO. Low concentrations of OTA (10 - 100 uM) enhanced glomerular and tubular glucose metabolism to CO[2] and only high concentrations of the mycotoxin (1000 uM) caused significant inhibition of glomerular and proximal tubular linolenic acid metabolism.

No description available.

Postpartum depression is a serious mental illness with onset of symptoms appearing anytime within the first four months after delivery (e.g. irritability, severe sadness, profound feelings of hopelessness, etc.). Environmental toxicants are synthetic (i.e. manufactured) or naturally found chemicals that are not produced by organisms as a result of cellular metabolism (e.g. tobacco smoke, pesticides, etc.). There is limited consideration for how exposure to environmental toxicants can create adverse psychological health effects, specifically postpartum depression. The purpose of this systematic review was to determine if the literature supports a link between exposure to environmental toxicants during the prenatal/perinatal period and postpartum depression and if so, to identify whether there are specific classes of toxicants that provide a higher risk for postpartum depression. Several databases were used to search the online literature, with the following inclusion criteria: articles published in English, publication years between 1995-2018, and with women of reproductive age (15-49 years old). The article selection process comprised of screening each article by title/abstract, followed by screening those articles based on full-text. Six categories of toxicants were identified among the thirty included articles. Active/passive smoke exposure was largely found to increase the risk of developing postpartum depression; dietary supplements provided mixed results; antidepressants demonstrated preventative effects; particulate air pollution was found to be associated with postpartum depression; oral contraceptives (DMPA) exhibited an increase in postpartum depressive symptoms; and organochlorine pesticides had no associative risk. Quality assessments were performed for all of the included articles, with the majority being assessed as satisfactory. This systematic review presents as a foundation for encouraging future research to investigate the link between environment and mental health, in order to attain a greater perspective.

The prospect of utilizing the cichlid teleost tilapia (Oreochromis niloticus) as an alternative experimental model to mammals for immunotoxicity risk assessment is currently being proposed. As such, the National Toxicology Program's (NTP) standard battery of rodent immunotoxicity assays is being developed for use in this fish species. Included in the testing series are the hemolytic plaque forming cell (PFC) and the cytotoxic T-lymphocyte (CTL) assays, quantitative indicators of antibody production and cell-mediated activity, respectively. The assays were modified in consideration of specific tilapian immune parameters, then tested using fourteen environmental contaminants or drugs, ten of which are classified by the NTP as immunotoxic in rodents. Reduced antibody production via a decrease in plaque number was observed in response to exposure of tilapia to eight of the nine humoral immunotoxicants, and five of the five non-immunotoxicants. Under specific immunization circumstances, immunostimulation (also a response to immunotoxicity) was noted via an increase in plaque number in benzo[a]pyrene (B[a]P) exposed fish using the PFC assay, a result noted in rodents as well. Reduced T-cell recognition and lysis of allogeneic tilapian lymphocytes via a decrease in the percentage of specific 51Chromium (51Cr) release was observed in response to exposure of tilapia to the nine of the ten cell-mediated immunotoxicants, and four of the four non-immunotoxicants. Although the normal teleost immune responsiveness was slightly weaker than seen with mice under comparable conditions (presumably due to differences in antibody structure and decreased cells counts), tilapia were found to exhibit well-defined humoral and cell-mediated immune responses, and responses to immunotoxic and non-immunotoxic chemicals comparable to the rodent model. / Master of Science

There is a need for a sensitive, specific, rapid and cost-effective assay that can be used as an early warning signal of contamination of aquatic ecosystems. The purpose of this work was to develop a sensitive stress-specific microbial bioreporter responsive to pro-oxidants. Furthermore, the bioreporter was designed to be applicable in environments possibly affected by metal processing activities. An E.coli bioreporter was developed containing a plasmid with the katG promoter sequence as the sensing sequence and with mCherry as the reporter protein. The bioreporter responded to metal pro-oxidants (Cd, As, Zn, Pb, Ag and Ag nanoparticles). A new assay growth-medium was developed and contributed to improve the sensitivity of our assay that has the best detection limit to inorganic pro-oxidants compared to other oxidative-stress sensitive bioreporters in the literature. The bioreporter detected pro-oxidants in environmental samples. The assay has a reasonable sensitivity, however, it still lacks sensitivity to detect pro-oxidants at concentrations lower than those shown to be toxic to many aquatic species. Within-lab reproducibility and robustness were determined to be acceptable. For stress-specific bioreporters to be incorporated in regulative legislations and industrial monitoring programs there is a need to improve the sensitivity of these assays, they need to be calibrated with other relevant pro-oxidants, inter-lab reproducibility needs to be established and robustness to environmental samples needs to be further tested. To further validate the sensitivity and ecotoxicological relevance of the bioreporter as a relevant predictive tool, stress-specific bioreporter assays need to be performed in parallel with traditional ecotoxicological assays using contaminated environmental samples.

Clinical research is needed to understand how cigarette toxicant yield affects smoker toxicant exposure. While there is much clinical research on yield and exposure in developed countries, there is little in developing countries. Forty smokers completed one, 4-hour session to compare yield and exposure of different cigarettes. Participants smoked three cigarettes under controlled topography conditions: one U.S. 111 flavor, one U.S. ultra light, and one Syrian cigarette, with 90 minutes between cigarettes. Sessions differed by Syrian brand; 21 participants smoked Alhamraa while 19 smoked A1 Sham cigarettes. Blood nicotine and breath CO samples were obtained, HR was monitored and subjective withdrawal and cigarette effect questions were asked. Results suggest that Syrian Alhamraa and U.S. full flavor were similar in exposure while Syrian A1 Sham and U.S. ultra light were similar. Though U.S. full flavor and ultra light cigarettes differed in toxicant yield and exposure, subjective ratings of withdrawal were similar.

This study’s purpose is to examine the potential relationships between MS (Multiple Sclerosis) and environmental outdoor air pollutants in GA (Georgia). We used secondary, cross-sectional data received from the member’s list of the National Multiples Sclerosis Society’s GA chapter (NMSS-GA), the U.S. census, and scorecard.org, a database based on the U.S. Environmental Protection Agency (EPA) Toxic Release Inventory (to 2002) and National Emissions Inventory (1999) data. The study population was 9,072,576 including 6,247 self-reported MS cases from NMSS-GA. Using stepwise multivariate linear regression of census and EPA data, the best predictive model in GA for female or total prevalence rates used per capita income and coarse particles (PM-10); male prevalence rates included only per capita income. The relationship between MS and PM-10 could be facilitated by influences of PM-10 on the systemic immune response and inflammation. More exposure and basic and clinical research are needed to understand environmental influences on MS.

Sea Turtles are long-lived marine reptiles that have existed for more than 150,000 years. All seven turtle species extant today are characterised as endangered by the World Conservation Union Red List of Threatened Species. This PhD thesis investigates aspects of endocrinology and toxicology in green (Chelonia mydas) (Peninsular Malaysia) and flatback (Natator depressus) (Curtis Island, Queensland, Australia) turtles. This thesis aimed to identify if toxicants have an affect on reproduction and development in marine turtles. A high affinity steroid binding protein showing an affinity for testosterone and oestradiol was identified and described in nesting C. mydas and the thermal profile of sex steroid binding proteins in C. mydas was studied. This is the first study that has investigated sex steroid binding proteins in marine turtles. A sex steroid binding protein was also observed in male and female hatchling C. mydas and the effect of temperature on sex steroid binding proteins was investigated. This new, minor-invasive method of sex identification shows that different sex steroid binding proteins could reflect different hormonal patterns in female and male hatchling C. mydas. The steroid and metabolites profiles in nesting C. mydas (Peninsular Malaysia) and N. depressus (Curtis Island, Queensland) were established. Progesterone levels were the highest followed by testosterone, oestrone and dihydrotestosterone levels. The significant role of oestrone in nesting sea turtles was verified. The elevated concentrations of corticosterone, thyroxine, glucose and triglyceride indicated high metabolic demands placed upon C. mydas and N. depressus during nesting activities. The metabolite profiles and hormone concentrations were investigated to determine whether there was any relationship between hormonal changes during nesting activities in C. mydas and N. depressus. A methodology to measure heavy metal concentrations in the blood and eggs of N. depressus was developed. Moreover, this was the first time that tin compound derivatives have been identified in marine turtles in Australia. A complex heavy metal profile was identified in eggs. It is suggested that eggs may be an important, practical and reliable indicator of environmental contamination in nesting marine turtles. Pesticides were measured in the blood and eggs of N. depressus. Organochlorine and polychlorinated biphenyl concentrations were measured in the blood in N. depressus. Traces of OCs and PCBs were detected in eggs of N. depressus. Furthermore, the effects of heavy metals in developing C. mydas of both sexes are presented. During development, it was investigated whether heavy metal concentrations were affected by age, gender or the different clutch in C. mydas. The effect of a variety of toxicants (i.e. pesticides and heavy metals) on the sex steroid binding protein properties was investigated in nesting C. mydas. This important study identifies mechanisms by which toxicants may exert a physiological effect upon sex steroids (i.e. testosterone and oestradiol) in nesting turtles. The toxicants were studied at a wide range of concentrations. Some toxicants were shown to weaken or abolish the association of the testosterone and/or oestradiol binding proteins in nesting C. mydas. Correlations were observed between heavy metal concentrations found in blood and eggs and steroid and metabolite levels in nesting N. depressus. Zinc which was previously measured in the blood was positively correlated with testosterone concentrations in nesting N. depressus. Chromium which was found in eggs was negatively correlated corticosterone concentrations. Manganese was the only heavy metal (measured in eggs) which was negatively correlated with progesterone and positively correlated with triglyceride concentrations in nesting N. depressus. Finally, a quantified histological method was developed to determine the sex in C. mydas hatchlings by investigating specific histological criteria. A number of “undetermined sex” hatchlings were verified and it is hypothesised that abnormal reproductive development is related to the presence of environmental contaminants previously found in the studied C. mydas population of Peninsular Malaysia.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental toxicants found in anthropogenic mixtures such as crude oil, air pollution, vehicle exhaust, and in some natural combustion reactions. Single PAHs such as benzo[a]pyrene (BaP) also impact fish behavior when animals are exposed in early life stages and for short periods of time. Aquatic animals such as fish may encounter BaP through road runoff and oil spills, but few studies have examined the impact of aqueous exposure on adult fish, and fewer have examined the resulting fitness-relevant behavioral consequences of BaP and PAH mixtures and their long-term persistence. This dissertation targets this gap in the literature by examining how aqueous exposure to BaP influences anxiety-like behavior, learning, and memory in adult zebrafish, and how parental exposure to the PAH mixture, crude oil, combined with hypoxia affects social and exploratory behavior in unexposed larval zebrafish. We found that learning and memory were not affected by 24 hour exposure to BaP, that anxiety-like behavior was minimally affected, and that locomotor parameters such as distance moved and times spent in darting and immobile states were significantly altered by exposure to BaP. Additionally, we found that parental exposure to crude oil and hypoxia decreased larval velocity. Additionally, we examined how crude oil, BaP, and the detergent COREXIT influence a monolayer of mouse and fish endothelial cells, as an in vitro blood-brain barrier (BBB) model. We found that exposure to BaP in particular caused significant damage to both fish and mammal in vitro BBB models, and damage to the BBB is one potential mechanism by which neural integrity and behavior may be influenced. Understanding how these toxicants influence fish brains and behavior will give insight into how fish populations explore and interact with their environment and with predators, and how these interactions persist even when toxicants are no longer present.